Dynamic loss of surface-expressed AMPA receptors in mouse cortical and striatal neurons during anesthesia.

Dynamic loss of surface-expressed AMPA receptors in mouse cortical and striatal neurons during anesthesia.
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DOI:
10.1002/jnr.22749
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发表时间:
2012-01
影响因子:
4.2
通讯作者:
Wang, John Q.
Wang, John Q.
中科院分区:
医学3区
文献类型:
--
作者:
Carino, Charlene;Fibuch, Eugene E.;Mao, Li-Min;Wang, John Q.

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离子型谷氨酸受体,特别是α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体亚型,在表面膜和细胞内细胞器之间进行动态运输。这种贩运活动决定了兴奋性突触的功效和强度,并受到突触输入变化的调节。鉴于中枢神经系统中的谷氨酸受体可能是麻醉剂的敏感目标,本研究调查了麻醉对成年小鼠脑神经元体内 AMPA 受体的运输和亚细胞表达的可能影响。我们发现全身注射戊巴比妥诱导的麻醉不会改变皮质神经元中三个 AMPA 受体亚基 (GluR1-3) 的总蛋白水平。然而,麻醉剂量的戊巴比妥会减少表面池中的 GluR1 和 GluR3 蛋白,并升高皮质神经元细胞内池中的这些蛋白质。在小鼠纹状体神经元中观察到类似的 GluR1/3 重新分布。戊巴比妥没有显着改变两个池中的 GluR2 表达。麻醉剂量的水合氯醛还可以降低表面 GluR1/3 表达并增加这些蛋白质的细胞内水平。戊巴比妥对 AMPA 受体亚细胞分布的影响是可逆的。麻醉消退后,改变的 GluR1/3 亚细胞分布恢复到正常水平。这些数据表明,戊巴比妥和水合氯醛诱导的麻醉可以改变皮质和纹状体神经元中的 AMPA 受体运输。这种改变的特点是在各自的表面和细胞内池中同时丢失和添加 GluR1/3 亚基。
Ionotropic glutamate receptors, especially the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtype, undergo dynamic trafficking between the surface membrane and intracellular organelles. This trafficking activity determines the efficacy and strength of excitatory synapses and is subject to modulation by changing synaptic inputs. Given the possibility that glutamate receptors in the central nervous system might be a sensitive target of anesthetic agents, this study investigated the possible impact of anesthesia on trafficking and subcellular expression of AMPA receptors in adult mouse brain neurons in vivo. We found that anesthesia induced by a systemic injection of pentobarbital did not alter total protein levels of three AMPA receptor subunits (GluR1–3) in cortical neurons. However, an anesthetic dose of pentobarbital reduced GluR1 and GluR3 proteins in the surface pool and elevated these proteins in the intracellular pool of cortical neurons. The similar redistribution of GluR1/3 was observed in mouse striatal neurons. Pentobarbital did not significantly alter GluR2 expression in the two pools. Chloral hydrate at an anesthetic dose also reduced surface GluR1/3 expression and increased intracellular levels of these proteins. The effect of pentobarbital on subcellular distribution of AMPA receptors was reversible. Altered subcellular distribution of GluR1/3 returned to normal levels after the anesthesia subsided. These data indicate that anesthesia induced by pentobarbital and chloral hydrate can alter AMPA receptor trafficking in both cortical and striatal neurons. This alteration is characterized by the concurrent loss and addition of GluR1/3 subunits in the respective surface and intracellular pools.
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